Retinoblastoma protein activation of interleukin 8 expression inhibits tumor cell survival in nude mice

Loss of retinoblastoma protein (Rb) has been implicated in the formation of a variety of human malignancies. Restoration of Rb expression in the cell lines representing these tumors eliminates or significantly reduces tumorig enicity in nude mice, but the mechanism for this Rb effect is unknown. Resu lts from this study indicated that Rb expression reduced tumor cell surviva l in nude mice by dramatically enhancing interleukin 8 (IL-8) secretion. IL -8 secreted by the Rb-transformed cells attracted neutrophils in vitro and tumor-infiltrating neutrophils in vivo, which is consistent with the Rb-med iated tumor regression being dependent on IL-8. The apparent, contradictory roles of IL-8 as a protumorigenic and antitumorigenic cytokine are discuss ed.